46 MUTATIONS 



I should say that this number must be very large. If you have, for 

 example, 10^^ stem cells and 10^^ erythrocytes, and clone size inter- 

 vening is about 100, then you have the products of all these 10^^ clones 

 in the circulation; even with large individual clonal variances, no 

 variation from time to time would be observed. Does that answer your 

 question? 



Goldstein: Yes. 



Atwood: I want to consider now what assumptions one would have 

 to make to still preserve the notion that the exceptional cells found in 

 people by isotope-dilution methods are products of mutational events 

 taking place at various times in the erythropoietic tissue. 



First of all, since we have essentially no age effect, we would have 

 to make the assumption that the main population of mutant stem lines 

 is established very early. We could also ask whether the rate of muta- 

 tion per cell division during this early period is higher than it is later. 

 As you recall, we estimated the number of divisions preceding the 

 steady state condition to be about the same as you have in ten years 

 during the steady state. If the mutation rate per division is the same 

 at all times, about ten years' worth of mutants would be established 

 during the early period. 



If the mutation rate per division is itself dependent on the division 

 rate, which is much higher in the early period, then a still higher 

 proportion of the mutants would be established early, and that is what 

 the limited data we now have seem to suggest. 



The second thing is that in order to regard the exceptional red cell 

 data as meaningful in this context, the lack of independence of the 

 alleles would have to be explained. 



I want to discuss both of these points in sequence. The first one is 

 the reason for bringing up the shell mosaics in mussels. 



I happened to notice, while eating some mussels [Mytilus edulis) , 

 that the population was polymorphic. In certain populations, some 

 individuals are unable to form the blue pigment that is normally in 

 the shell. Something less than 1 per cent (I don't know the frequency) 

 of mussels in the area of Woods Hole, Massachusetts, are deficient in 

 pigment, but about 60 per cent of these have one or more blue sectors 

 in the shell that could be interpreted as reversions to the ability to 

 fomi pigment. 



The umbo is the point of origin of the shell. One sees concentric 

 growth rings from which one can deduce the size and shape that the 

 animal must have had in the past, and the revertant sectors cut across 

 these, from the umbo to the periphery. The shell-forming gland is a 



